This invention relates to a method of dynamic nuclear polarisation (Overhauser) enhanced magnetic resonance imaging (OMRI).
Magnetic resonance imaging (MRI) is a diagnostic technique that has become particularly attractive to physicians as it is non-invasive and does not involve exposing the patient under study to potentially harmful radiation such as X-rays.
Conventional Overhauser enhanced MRI has been primarily reported in the context of electron spin resonance enhanced magnetic resonance imaging (ESREMRI, PEDRI or OMRI). This is a method of MRI in which enhancement of the magnetic resonance signals (often by a factor of a hundred or more) from which images may be generated is achieved by virtue of dynamic nuclear polarization (the Overhauser effect) that occurs on VHF stimulation of an ESR transition in a material in the subject under study.
In the basic in vivo OMRI technique, dynamic nuclear polarization results in an increase in the population difference between the excited and ground nuclear spin states of selected nuclei, generally protons, which are responsible for the magnetic resonance signals. Since MR signal intensity is proportional to this population difference, the subsequent stages of each imaging sequence, performed essentially as in conventional MRI techniques, result in larger amplitude MR signals being detected.
OMRI enhancement agents (frequently simply referred to as contrast agents) which exhibit an ESR transition able to couple with an NMR transition of the MR imaging nuclei may be naturally present within the subject (eg. oxygen or melanin) or may be administered thereto. OMRI enhancement agents have been reported in inter alia WO-A-88/10419 (Hafslund Nycomed Innovation AB), WO-A-90/00904 (Hafslund Nycomed Innovation AB), WO-A-91/12024 (Nycomed Innovation AB) and WO-A-93/02711 (Hafslund Nycomed Innovation AB). Most of the OMRI enhancement agents disclosed to date are radicals (eg. organic free radicals) and their use in vivo is constrained by their inherent instability and toxicity. It will often be the case that a radical found to give excellent ESR enhancement factors in vitro cannot be used diagnostically due to its physiological incompatibility. There is therefore a need for improved methods of OMRI which are more flexible, i.e. less constrained by physiological factors.
U.S. Pat. No. 5,545,396 (Albert) discloses an in vivo MR imaging method in which a noble gas (eg. 129Xe or 3He) having a hyperpolarised nuclear spin is inhaled into the lungs and a representation of its spatial distribution therein is generated. MR imaging of the human oral cavity using hyperpolarised 129Xe was also reported by Albert in J. Mag. Res., 1996: B111, 204-207. Naturally the technique disclosed by Albert is unsuitable for administration routes other than inhalation and is therefore of limited utility in MR imaging. Its use is also subject to the physiological problems associated with in vivo administration of a noble gas.
Research Disclosure No. 348, 1993, page 242 discloses an Overhauser enhanced MRI imaging technique wherein the electron paramagnetic resonance of a free radical is irradiated under the right conditions so as to enhance the NMR signal.
The present invention is based on a method of MRI of a sample in which it is possible to avoid administering the whole of, or substantially the whole of, an OMRI enhancement agent to the sample, whilst still achieving a desired Overhauser enhanced contrast effect. The method relies on ex vivo dynamic nuclear polarisation of selected nuclei of an MR imaging agent by a hyperpolarised gas, the latter conveniently being separated from the MR imaging agent prior to administration of the polarised MR imaging agent into the sample (eg. the subject).